Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis

Sohail Hussain; Mohammed Ashafaq; Saeed Alshahrani; Rahimullah Siddiqui; Rayan A Ahmed; Gulrana Khuwaja; Fakhrul Islam

doi:10.1016/j.toxrep.2020.09.008

Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis

Toxicol Rep. 2020 Sep 17:7:1296-1304. doi: 10.1016/j.toxrep.2020.09.008. eCollection 2020.

Authors

Sohail Hussain¹, Mohammed Ashafaq¹, Saeed Alshahrani¹, Rahimullah Siddiqui¹, Rayan A Ahmed¹, Gulrana Khuwaja², Fakhrul Islam¹

Affiliations

¹ Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Saudi Arabia.
² Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, Saudi Arabia.

Abstract

Acetaminophen (APAP) is used as a primary drug due to its antipyretic and analgesic activity. The mechanism of action of APAP toxicity in the liver is due to the depletion of glutathione which elicited free radicals generation. Therefore, the objective of our work is to investigate the APAP induced liver damage and its repair by free radical scavenging activity of cinnamon oil (CO) in male Wistar rats. To investigate the effects of CO at different doses (50, 100 and 200 mg/kg b.w.), animals were given a single oral dose of CO per day for 14 days between 12:00-1:00 PM. The biochemical changes, imbalance in oxidative markers, interleukins, caspases and histopathological studies were determined for quantifying the hepatoprotective effect of CO. One dose of APAP (2 g/kg b.w.) results in significant hepatotoxicity and marked increase the serum markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin, total protein, content of lipid peroxidation (LPO), interleukins (IL-1β, IL-6), caspase-3, -9 expression, DNA fragmentation and histopathological changes were observed. Significant decrease in the levels of LPO, interleukins IL-1β, IL-6, caspase-3, -9 expressions, qualitative as well as quantitative determination of DNA fragments and histopathological changes were reversed by the administration of CO dose dependently. Furthermore, it also restores the depleted activity of antioxidative enzymes. Our study shows that an imbalance in the oxidative parameter in the liver by APAP is restored by treating the animals with CO.

Keywords: ALP, alkaline phosphatase; ALT, alanine aminotransferase; ANOVA, analysis of variance; APAP, N-acetyl-p-aminophenol; AST, aspartate aminotransferase; Acetaminophen; BHA, butylated hydroxyanisole; CO, cinnamon oil; Cinnamon oil; DNA fragmentation; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, glutathione; Hepatotoxicity; LPO, lipid peroxidation; MDA, malondialdehyde; MEC, molar extinction coefficient; NAPQI, N-acetyl parabenzoquinoneimine; Oxidative stress; PMS, post mitochondrial supernatants; SOD, superoxide dismutase.